Immunology

Kristine Krafts, M.D.Overview

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Immunology Overview

Definitions

Definitions

• Immunity = protection against infections

• Immune system = collection of cells and molecules that defend us against microbes

• Immune deficiencies → infections

• Immune excesses → autoimmune diseases

Innate (Natural) Immunity

• Always present (innate); doesn’t change over time

• First line of defense when bugs come

• Major components:• Epithelial barriers (skin, GI, respiratory)• Phagocytes • NK cells• Complement

Adaptive (Acquired) Immunity

• Second line of defense

• More specific (adaptive) and powerful than innate

• Major components:• Lymphocytes• Lymphocyte products (like antibodies)

• Two types of adaptive immunity:• Humoral immunity (mediated by antibodies)• Cellular immunity (mediated by T cells)

Immunology Overview

Definitions

Cells• Lymphocytes

White Blood Cell Development

White blood cells

Lymphocytes

• Present in lymphoid organs and in blood

• Groups• T-lymphocytes (grow up in thymus)• B-lymphocytes (grow up in bone marrow)

• Each one has receptors for a specific antigen!

Lymphocyte (could be B cell or T cell!)

• Lymphocytes grow up in primary organs, then travel to secondary organs, where they get exposed to antigens.

• Primary organs• Thymus• Bone marrow

• Secondary organs• Lymph nodes• Spleen• Mucosal and cutaneous lymphoid tissues

Lymphoid Tissues

B cells are in follicles; T cells are in interfollicular areas

Lymph Node

T Lymphocytes

• Two basic functions:• Kill stuff (cytotoxic T cells)• Help other cells do their jobs (helper T cells)

• T-cell receptor (TCR) complex recognizes antigens• Binds antigen• Sends signals to the T cell

• Antigens must be:• Displayed by other cells…• …AND bound to an MHC molecule (receptor)

Cytotoxic T cells surrounding tumor cell

The T-Cell Receptor Bound to AntigenAntigen-presenting cell

T cell

Class I MHC moleculeClass II MHC molecule

class II MHC genes class I MHC genesclass III MHC genes

Major Histocompatibility Complex (MHC)

Class I and II MHC Molecules

Class I molecules

• Display antigens from within the cell (e.g., viral antigens) to cytotoxic (CD8+) T cells.

• Present on all nucleated cells! (Good idea.)

Class II molecules

• Display extracellular antigens (e.g., bacterial antigens the cell has eaten) to helper (CD4+) T cells.

• Present only on antigen-presenting cells, like macrophages! (Makes sense.)

B Lymphocytes

• Basic function: make antibodies

• B-cell receptor complex recognizes antigens• Binds antigen• Sends signals to B cells

• Antigens can be free and circulating (don’t have to be bound to MHC molecules or displayed by other cells to be recognized!)

Natural Killer (NK) Cells

• Belong to innate immunity arm

• Receptors are not highly variable (like T and B cell receptors are)

• Main job: recognize and kill damaged or infected cells

Natural killer cell

Natural killer cell (top) killing infected cell (bottom)

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Antigen-Presenting Cells

Dendritic cells• Present mostly in two places: under epithelia and in

germinal centers of lymph nodes• Capture bug, present antigens to B and T cells• Super important in activating the adaptive system

Macrophages

• Present all over the body• Eat bugs and present antigens to T cells• Their role in activating the adaptive system is not as

pivotal though!

Dendritic cell surrounded by lymphocytes

Dendritic cell (right) talking to lymphocyte (left)

MacrophageMonocyte

Macrophage reaching for bacterium

Macrophage gorging on bacteria

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response

The Innate Immune Response

• If bugs make it through epithelium, they encounter cells of the innate immune system

• What happens in the innate immune system?• Phagocytes eat bugs• Complement is activated • NK cells find and kill infected cells • Dendritic cells migrate to lymph nodes to

activate the adaptive immune system

What is complement?Just give me the bottom line.

It’s a bunch of proteins that poke holes in cells.

Okay, give me a little more information.

• Consists of about 20 plasma proteins (C1, C2, etc.)

• Can be activated by bacterial components

• Activation proceeds in a cascade fashion

• End results:• Cell lysis• Chemotaxis (attraction of neutrophils)• Opsonization (coating of cells to make them

“yummy” to macrophages)

Complement, ridiculously oversimplified

Immunology OverviewDefinitions

Cells• Lymphocytes • Antigen-presenting cells• Effector cells

Responses• The innate immune response• Capturing and displaying antigens

Capturing and Displaying Antigens

• Dendritic cells in epithelium capture bug antigens, transport them to lymph nodes

• Dendritic cells display antigens to B and T cells

• Antigens and cytokines trigger proliferation and differentiation of B and T cells

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity

The Main Players in Cell-Mediated Immunity

Helper (CD4+) T cells• These guys help macrophages eat bugs.• They also call in neutrophils.

Cytotoxic (CD8+) T cells• These guys kill infected cells.• They are like highly-trained assassins.

Matt Damon and the “asset”

Cell-Mediated Immunity

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity

Humoral Immunity

Bacteria enter body

B cells make antibodies against

bacteria

Antibodies bind to bacteria

Phagocytes ingest bacteria

What is an antibody?

• Y-shaped glycoprotein • 2 light chains (κ or λ)• 2 heavy chains (α, γ, δ, ε, or μ)

• Fab fragments• Upper part of Y (the arms)• Binds to antigen

• Fc fragment• Lower part of Y (the stem)• Binds to cells like macrophages, neutrophils.

What happens when antibodies bind to bugs?

• Bugs are neutralized (they can’t infect cells).

• Antibody-coated bugs are “opsonized,” making them yummy to macrophages and neutrophils (which have receptors for the Fc portion of IgG! How handy!).

• Complement is activated (bad news for bugs).

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Immunologic Memory

• After an infection is over, most immune cells die.

• A few memory cells remain and live on for years.• Expanded pool of antigen-specific lymphocytes• Respond faster, better than naïve lymphocytes• Vaccines depend on these guys

Summary of the Adaptive Immune Response

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory

Summary of the Adaptive Immune Response

Immunology Overview

Definitions

Cells• Lymphocytes • Antigen-presenting cells

Responses• The innate immune response• Capturing and displaying antigens• Cell-mediated immunity• Humoral immunity• Immunologic memory